Variant 19-2916233-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173480.3(ZNF57):c.286C>T(p.His96Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF57
NM_173480.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.04

Variant links:

Genes affected

ZNF57 (HGNC:13125): (zinc finger protein 57) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF57 links:

ENSG00000253392 (HGNC:):

ENSG00000253392 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061979026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF57	NM_173480.3 linkuse as main transcript	c.286C>T	p.His96Tyr	missense_variant	3/4	ENST00000306908.10	NP_775751.1	Q68EA5A5HJR3
ZNF57	NM_001319083.2 linkuse as main transcript	c.190C>T	p.His64Tyr	missense_variant	3/4		NP_001306012.1	Q68EA5G3V131A5HJR3B4DXX0
ZNF57	XM_011527682.3 linkuse as main transcript	c.190C>T	p.His64Tyr	missense_variant	3/4		XP_011525984.1	G3V131

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF57	ENST00000306908.10 linkuse as main transcript	c.286C>T	p.His96Tyr	missense_variant	3/4	1	NM_173480.3	ENSP00000303696.5		Q68EA5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453504

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723006

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2022

The c.286C>T (p.H96Y) alteration is located in exon 3 (coding exon 3) of the ZNF57 gene. This alteration results from a C to T substitution at nucleotide position 286, causing the histidine (H) at amino acid position 96 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.6

DANN

Benign

0.42

DEOGEN2

Benign

0.0047

T;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.31

T;T;T;T

M_CAP

Benign

0.00098

MetaRNN

Benign

0.062

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

L;.;.;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

N;N;N;.

REVEL

Benign

0.076

Sift

Benign

0.58

T;D;T;.

Sift4G

Benign

0.51

T;T;T;T

Polyphen

0.32

B;.;.;.

Vest4

0.18

MutPred

0.32

Loss of disorder (P = 0.0439);.;.;.;

MVP

0.19

MPC

0.032

ClinPred

0.063

GERP RS

1.2

Varity_R

0.040

gMVP

0.067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over